{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:27:28Z","timestamp":1790872048601,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2008400"],"award-info":[{"award-number":["2020YFC2008400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with sepsis may progress to acute respiratory distress syndrome (ARDS). Evidence of neutrophil extracellular traps (NETs) in sepsis-induced lung injury has been reported. However, the role of circulating NETs in the progression and thrombotic tendency of sepsis-induced lung injury remains elusive. The aim of this study was to investigate the role of tissue factor-enriched NETs in the progression and immunothrombosis of sepsis-induced lung injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human blood samples and an animal model of sepsis-induced lung injury were used to detect and evaluate NET formation in ARDS patients. Immunofluorescence imaging, ELISA, Western blotting, and qPCR were performed to evaluate <jats:italic>in vitro<\/jats:italic> NET formation and tissue factor (TF) delivery ability. DNase, an anti-TF antibody, and thrombin inhibitors were applied to evaluate the contribution of thrombin to TF-enriched NET formation and the contribution of TF-enriched NETs to immunothrombosis in ARDS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significantly increased levels of TF-enriched NETs were observed in ARDS patients and mice. Blockade of NETs in ARDS mice alleviated disease progression, indicating a reduced lung wet\/dry ratio and PaO2 level. <jats:italic>In vitro<\/jats:italic> data demonstrated that thrombin-activated platelets were responsible for increased NET formation and related TF exposure and subsequent immunothrombosis in ARDS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The interaction of thrombin-activated platelets with PMNs in ARDS patients results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during thrombosis may offer novel therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.677902","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T12:38:34Z","timestamp":1626266314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Tissue Factor-Enriched Neutrophil Extracellular Traps Promote Immunothrombosis and Disease Progression in Sepsis-Induced Lung Injury"],"prefix":"10.3389","volume":"11","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuainan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wankun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhong","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1158\/0008-5472.CAN-05-2502","article-title":"Matrix Metalloproteinase-9 From Bone Marrow-Derived Cells Contributes to Survival But Not Growth of Tumor Cells in the Lung Microenvironment","volume":"66","author":"Acuff","year":"2006","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3109\/07388551.2015.1128876","article-title":"Flow Cytometry: Basic Principles and Applications","volume":"37","author":"Adan","year":"2017","journal-title":"Crit. 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